Original research articleA 1-year randomized study to evaluate the effects of a dose reduction in oral contraceptives on lipids and carbohydrate metabolism: 20 μg ethinyl estradiol combined with 100 μg levonorgestrel
Introduction
Since the introduction of combined oral contraceptives (COCs) in the early 1960s, considerable efforts have been made to reduce the dose of the hormonal components in order to minimize the risk of adverse events (AEs). These efforts attempted to reduce the hormone content according to the principle “as little as possible, but as much as necessary.” In the 1990s, two new 20-μg ethinyl estradiol (EE)-containing preparations were introduced, one with the progestogen gestodene [1] and the other with desogestrel [2]. Both were derived from already marketed preparations containing 30 μg EE without reducing the progestogen dose. Another investigation, carried out with injectable contraceptives [3], suggested that the ratio between both hormonal components could influence the pharmacodynamic properties of the preparations. The new preparation tested in our study was also derived from an existing oral contraceptive containing 30 μg EE combined with 150 μg levonorgestrel (LNG), which was proven safe and effective for some decades [4]. However, in the new preparation, the dosages of both EE and LNG were reduced by one third. This dose reduction of both components maintains the original preparation's estrogen/progestogen ratio.
A large body of clinical data based on low-dose OCs containing 20 μg EE has become available in the past years. Despite some initial doubts about this reduction in the estrogen dose, it is generally acknowledged that 20 μg EE, in combination with a suitable progestogen, can provide effective contraceptive protection and clinically acceptable cycle control [1], [2], [5], [6], [7].
However, limited data on the effect of 20 μg EE COCs on metabolic variables is available [8], [9], [10]. The preparation investigated here is the first with a ‘balanced’ reduction, that is, a reduction of both hormonal components by one third. In this paper, we present the findings of the lipid and carbohydrate investigations. The results of the hemostatic variables will be published elsewhere. Recently, a very similar study was published which was conducted in The Netherlands [11].
Section snippets
Materials and methods
The study was performed as an open-label, randomized, prospective study at one center in Denmark (Department of Obstetrics and Gynecology, Frederiksberg Hospital, University of Copenhagen, DK 2000 Copenhagen F, Denmark) from December 1997 to April 2000 (study no. 96050). We compared the dose-reduced investigational preparation containing 20 μg EE and 100 μg LNG (20 EE) (Miranova, Schering, Berlin, Germany) with the reference containing 30 μg EE and 150 μg LNG (30 EE) (Microgynon, Schering). The
Results
A total of 70 women were randomized, 35 in each group. Sixty-nine received at least one dosage of treatment (full analysis population). Forty-nine women, 22 in the 20 EE/100 LNG group and 27 in the 30 EE/150 LNG group, were included in the PP population. The demographic characteristics of the two groups at baseline were well matched (see Table 1).
Discussion
This study was conducted to compare the differences in the effects of two COC preparations, one a dose-reduced version of the other, on lipid and carbohydrate profiles during 1 year of treatment in healthy volunteers.
The changes found in the lipid profile after 1 year of treatment are characteristic for low EE dose COCs [11], [14]: moderate, but measurable, increases in the values for LDL cholesterol, VLDL cholesterol and total triglycerides, and decreases in HDL2 cholesterol and Lp(a) were
Conclusion
Similar effects on the lipid and carbohydrate profiles were found for both preparations. The balanced one-third EE dose reduction in this new OC caused slightly lower, but insignificant, changes in the lipid and carbohydrate variables compared with the reference treatment.
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